Process for the preparation of n-alkylsulfonylaminosulfonylureas

ABSTRACT

Known herbicides of the formula (I) ##STR1## in which R 1  is alkyl, alkenyl or alkynyl, which are optionally substituted by halogen, alkoxy or alkoxycarbonyl, 
     R 2  is H, alkyl, alkenyl, alkynyl or cycloalkyl, 
     R 3  and R 4  are H or alkyl, 
     R 5  and R 6  are H, alkyl or alkoxy, each of which can be substituted by halogen, alkoxy or alkylthio, or are halogen, alkylthio, alkylamino or dialkylamino, 
     or, if R 2  or R 3  is H, their salts with bases, can be obtained when compounds of the formula II 
     
         R.sup.1 --SO.sub.2 --NR.sup.2 --SO.sub.2 --NR.sup.3 --CO--OR.sup.7(II) 
    
     in which 
     R 1 , R 2  and R 3  are as defined above, 
     are reacted with compounds of the formula III ##STR2## in which R 4 , R 5  and R 6  are as defined above and 
     R 7  is alkyl, haloalkyl or optionally substituted phenyl, 
     in an inert organic solvent, to give the compounds of the formula I.

The present invention relates to a process for the preparation of thecompounds of the formula I ##STR3## in which R¹ is (C₁ -C₆)-alkyl, (C₂-C₆)-alkenyl or (C₂ -C₆)-alkynyl, each of the 3 radicals mentioned beingunsubstituted or mono- or polysubstituted by radicals from the groupcomprising halogen, (C₁ -C₄)-alkoxy and [(C₁ -C₄)-alkoxy]carbonyl,

R² is hydrogen, (C₁ -C₆)-alkyl, (C₂ -C₆)-alkenyl, (C₂ -C₆)-alkynyl or(C₃ -C₆)-cycloalkyl,

R³ and R⁴ independently of one another are hydrogen or (C₁ -C₄)-alkyl,

R⁵ and R⁶ independently of one another are hydrogen, (C₁ -C₄)-alkyl or(C₁ -C₄)-alkoxy, the 2 last-mentioned radicals being unsubstituted ormono- or polysubstituted by radicals from the group comprising halogen,alkoxy and alkylthio, or are halogen, (C₁ -C₄)-alkylthio, (C₁-C₄)-alkylamino or (C₁ -C₄)-dialkylamino,

and, if R² and R³ are hydrogen, their physiologically acceptable saltswith bases.

Compounds of the formula I are known and are employed as plantprotection agents having a herbicidal action; see, for example, EP-A-0,131,258.

This publication also already refers to, or describes, a range ofprocesses by which compounds of the formula I can be prepared.

The disadvantage of the known processes is the relatively low yields ofnot more than 65-70%. As a consequence of these low yields, considerableamounts of contamination and by-products are produced. From anecological as well as an economical point of view, these describedprocesses cannot be carried out on a large scale, since the largeamounts of by-products and waste which would result thereby areunacceptable, and their disposal, for example by incineration, iscomplicated. Moreover, such low yield means that the loss of startingmaterials employed is drastic.

A novel process has now been found by which the compounds of the formulaI can be prepared in a surprisingly high yield and purity.

The process according to the invention is distinguished by the fact thatcompounds of the formula II

    R.sup.1 --SO.sub.2 --NR.sup.2 --SO.sub.2 --NR.sup.3 --CO--OR.sup.7 (II)

in which

R¹, R² and R³ are as defined above and

R⁷ is alkyl, haloalkyl or optionally substituted phenyl,

are reacted with compounds of the formula III ##STR4## in which R⁴, R⁵and R⁶ are as defined above,

in an inert organic solvent, to give the compounds of the formula I.

In the formulae mentioned and in the following text, alkyl, alkoxy,haloalkyl, alkylamino and alkylthio radicals as well as thecorresponding unsaturated and/or substituted radicals can, unlessotherwise indicated, in each case be straight-chain or branched as faras the carbon chain is concerned; alkyl radicals, also in the compoundmeanings such as alkoxy, haloalkyl, etc., are, for example, methyl,ethyl, n- or i-propyl, n-, i-, t- or 2-butyl; alkenyl and alkynylradicals have the meaning of the possible unsaturated radicals whichcorrespond to the alkyl radicals, such as 2-propenyl, 2- or 3-butenyl,2-propynyl, 2- or 3-butynyl; optionally substituted phenyl is, forexample, phenyl which is unsubstituted or substituted by one or more,preferably 1 to 3, radicals from the group comprising halogen, (C₁-C₄)-alkyl, (C₁ -C₄)-alkoxy, (C₁ -C₄)-haloalkyl, (C₁ -C₄)-thioalkyl, (C₁-C₄ -alkoxy)carbonyl, (C₁ -C₄ -alkyl)sulfonyl, cyano and nitro; halogen,also halo in haloalkyl etc., is fluorine, chlorine, bromine or iodine,preferably fluorine, chlorine or bromine.

Preferred processes amongst the processes according to the invention forthe preparation of the compounds of the formula I are those in which R¹and R² independently of one another are (C₁ -C₃)-alkyl or (C₁-C₃)-alkenyl, in particular (C₁ -C₂)-alkyl, R³ and R⁴ are hydrogen, R⁵and R⁶ independently of one another are (C₁ -C₂)-alkyl or (C₁-C₂)-alkoxy, in particular methyl or methoxy.

R⁷ is preferably (C₁ -C₄)-alkyl, (C₁ -C₄)-haloalkyl or phenyl, inparticular ethyl or phenyl.

As a rule, the yields in the process according to the invention are atleast 95% of theory, and the purities of the sulfonylureas I formed areusually higher than 98% by weight.

The process according to the invention is carried out in inert organicsolvents. Examples of types of solvents in this context are aromatic,optionally halogenated hydrocarbons and aprotic polar solvents such asdialkylalkanoylamides, dialkyl sulfoxides, polyalkylene glycol dialkylethers, N-alkylated cyclic amides and nitriles. Examples of preferredsolvents are toluene, xylene, chlorobenzene, dimethylformamide, dimethylsulfoxide, di-, tri- or tetraethylene glycol dialkyl ethers, inparticular di-, tri- or tetraethylene glycol dimethyl ether or di-, tri-or tetraethylene glycol diethyl ether, N-methylpyrrolidone,acetonitrile, and also mixtures of two or more of the solventsmentioned.

As a rule, the ratio of the compound of the formula II to the compoundof the formula III is equimolar or the former is employed in a slightexcess. A preferred molar ratio of II:III is from 1:1 to 1.2:1, inparticular 1:1 to 1.1:1.

It is an advantage of the process according to the invention that thesolvents can be recycled in virtually quantitative yield since theproducts of the formula I precipitate from the reaction medium in theform of sparingly soluble compounds in high purity and yield. Thesolvents can subsequently be purified, for example by distillation, andthen fed back into the production process.

The reaction temperatures range preferably from 0° C. up to the boilingpoint of the solvent employed, in particular from room temperature (forexample 20° C.) to 110° C.

The starting compounds of the formulae II and III which are required forthe preparation of the compounds according to the invention of thegeneral formula I can be prepared by processes known from theliterature.

For example, the compounds of the formula II are obtained analogously tocustomary methods (see, for example, Tietze und Eicher in "Reaktionenund Synthesen" [Reactions and Syntheses], p. 92, Thieme Verlag,Stuttgart 1981), by reacting the corresponding sulfonamides IV withchloroformic esters V,

    R.sup.1 --SO.sub.2 --NR.sup.2 --SO.sub.2 --NH--R.sup.3     (IV)

    Cl--CO--OR.sup.7                                           (V)

which, in turn, are accessible in very high yield by customarylaboratory methods (see, for example, "Organikum", 7th edition, p. 539,VEB Deutscher Verlag der Wissenschaften, Berlin 1967) by reacting thecorresponding sulfonamides VI with the corresponding sulfamoylchloridesVII

    R.sup.1 --SO.sub.2 --NH--R.sup.2                           (VI)

    Cl--SO.sub.2 --NH--R.sup.3                                 (VII)

The heterocycles of the formula III are either commercially available orcan be prepared easily by suitable laboratory methods; see, for example,U.S. Pat. No. 4,310,470; EP 0,024,200; U.S. Pat. No. 4,299,960; M. J.Langerman, C. K. Banks, JACS 73, 3011 (1951).

The process according to the invention must be regarded as particularlysurprising because the starting material of the formula II contains aplurality of activated electrophilic and nucleophilic centers, where inparticular the electrophilic centers could all react in principle withthe nucleophilic substances of the formula III and could therefore givea large number of by-products because of fragmentation reactions; cf.Beyer, Lehrbuch der org. Chemie [Textbook of Organic Chemistry], 19thedition, p. 128, Hirzel Verlag Stuttgart), according to which sulfonylgroups are very good leaving groups.

However, the secondary reactions mentioned surprisingly are virtuallynonexistent in the process according to the invention, because theprocess according to the invention usually gives yields of more than 95%of theory and purities of more than 98%.

The process according to the invention therefore represents a processfor synthesizing the compounds of the formula I in virtuallyquantitative yields which is novel and simple, and is easilyreproducible and highly selective, even on a larger, industrial scale.

The process can be carried out batchwise or continuously.

In the following test, the process according to the invention will beillustrated with the aid of a number of examples. Unless otherwisespecified, percentages are by weight.

EXAMPLE 11-[(N-Methylsulfonyl-N-methylamino)sulfonyl]-3-(4,6-dimethoxy-2-pyrimidyl)urea

52.0 g of ethyl (N-methylsulfonyl-N-methylamino)sulfonylcarbamate aredissolved in 500 ml of chlorobenzene, 31.0 g of2-amino-4,6-dimethoxypyrimidine are added at room temperature withstirring, and the mixture is heated at 80° C. for 3 hours. After coolingto 0° C., the precipitate is filtered off and washed with 100 ml ofchlorobenzene. 72.7 g of the desired product of a purity of 98.5% areobtained, which corresponds to a yield of 97.2% of theory. The meltingpoint of the product is 185°-186° C.

EXAMPLE 21-[(N-Methylsulfonyl-N-methylamino)sulfonyl]-3-(4-methoxy-6-methyl-2-pyrimidyl)urea

52.0 g of ethyl (N-methylsulfonyl-N-methylamino)sulfonylcarbamate aredissolved in 500 ml of chlorobenzene, 27.8 g of2-amino-4-methoxy-6-methylpyrimidine are added at room temperature, andthe mixture is heated at 50° C. for 5 hours. After cooling to 0° C., theprecipitate is filtered off. After washing with 100 ml of chlorobenzene,68.8 g of the desired product of a purity of 98.9% are obtained; thiscorresponds to a yield of 96.4% of theory. The melting point of theproduct is 118°-120° C.

EXAMPLE 31-[(N-Ethylsulfonyl-N-ethylamino)sulfonyl]-3-(4,6-diethoxy-2-pyrimidyl)urea

65.2 g of phenyl (N-ethylsulfonyl-N-methylamino)sulfonylcarbamate aredissolved in 700 ml of toluene, 36.6 g of 2-amino-4,6-diethoxypyrimidineare added at room temperature, and the mixture is heated at 110° C. for2 hours. After cooling to room temperature, the precipitate is filteredat 0° C. and washed with 200 ml of toluene. 82.6 g of the desiredproduct of a purity of 98.1% are obtained, which corresponds to a yieldof 95.3% of theory.

The melting point of the product is 174°-176° C.

The compounds of the formula I which are listed in Table 1 below can besynthesized analogously to Examples 1 to 3.

                                      TABLE 1                                     __________________________________________________________________________    Ex.                               M.p.                                        No. R.sup.1                                                                           R.sup.2 R.sup.3                                                                           R.sup.4                                                                           R.sup.5                                                                            R.sup.6                                                                            (°C.)                                __________________________________________________________________________     4  CH.sub.3                                                                          CH.sub.3                                                                              H   H   CH.sub.3                                                                           CH.sub.3                                                                           150-151                                      5  CH.sub.3                                                                          C.sub.3 H.sub.7                                                                       H   H   CH.sub.3                                                                           CH.sub.3                                                                           149-151                                      6  CH.sub.3                                                                          C.sub.3 H.sub.7                                                                       H   H   OCH.sub.3                                                                          CH.sub.3                                                                           141-143                                      7  CH.sub.3                                                                          CH.sub.2 ═CHCH.sub.2                                                              H   H   CH.sub.3                                                                           CH.sub.3                                                                           139-141                                      8  CH.sub.3                                                                          CH.sub.2 ═CHCH.sub.2                                                              H   H   OCH.sub.3                                                                          CH.sub.3                                                                           159-161                                      9  CH.sub.2 Cl                                                                       CH.sub.3                                                                              H   H   CH.sub.3                                                                           CH.sub.3                                                                           146-148                                     10  CH.sub.3                                                                          C.sub.3 H.sub.7                                                                       H   H   OCH.sub.3                                                                          OCH.sub.3                                                                          156-157                                     11  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                    H   H   OCH.sub.3                                                                          OCH.sub.3                                                                          121-123                                     12  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                    H   H   Cl   OCH.sub.3                                                                          153-155                                     13  C.sub.2 H.sub.5                                                                   C.sub.2 H.sub.5                                                                       H   H   OCH.sub.3                                                                          OCH.sub.3                                        14  CH.sub.3                                                                          CH.sub.3                                                                              CH.sub.3                                                                          H   OCH.sub.3                                                                          OC.sub.2 H.sub.5                                 15  CH.sub.3                                                                          CH.sub.3                                                                              H   CH.sub.3                                                                          OCH.sub.3                                                                          OCH.sub.3                                        16  CH.sub.3                                                                          C.sub.2 H.sub.5                                                                       CH.sub.3                                                                          CH.sub.3                                                                          C.sub.2 H.sub.5                                                                    OCH.sub.3                                        17  C.sub.3 H.sub.7                                                                   CH.sub.3                                                                              H   H   CH.sub.3                                                                           CH.sub.3                                         18  C.sub.4 H.sub.9                                                                   CH.sub.3                                                                              H   H   OCH.sub.3                                                                          OCH.sub.3                                        19  CH.sub.3                                                                          cyclo-C.sub.6 H.sub.11                                                                H   H   OCH.sub.3                                                                          OCH.sub.3                                        20  CH.sub.3                                                                          CH.sub.2 --C.tbd.CH                                                                   CH.sub.3                                                                          H   CH.sub.3                                                                           OCF.sub.2 H                                      21  CH.sub.3                                                                          CH.sub.2 --CO.sub.2 CH.sub.3                                                          H   H   CH.sub.3                                                                           CH.sub.3                                         __________________________________________________________________________

We claim:
 1. A process for the preparation of the compounds of theformula I ##STR5## in which R¹ is (C₁ -C₆)-alkyl, (C₂ -C₆)-alkenyl or(C₂ -C₆)-alkynyl, each of the 3 radicals mentioned being unsubstitutedor mono- or polysubstituted by halogen, (C₁ -C₄)-alkoxy and [(C₁-C₄)-alkoxy]carbonyl,R² is hydrogen, (C₁ -C₆)-alkyl, (C₂ -C₆)-alkenyl,(C₂ -C₆)-alkynyl or (C₃ -C₆)-cycloalkyl, R³ and R⁴ independently of oneanother are hydrogen or (C₁ -C₄)-alkyl, R⁵ and R⁶ independently of oneanother are hydrogen, (C₁ -C₄)-alkyl or (C₁ -C₄)-alkoxy, the 2last-mentioned radicals being unsubstituted or mono- or polysubstitutedby radicals from the group comprising halogen, alkoxy and alkylthio, orare halogen, (C₁ -C₄)-alkylthio, (C₁ -C₄)-alkylamino or (C₁-C₄)-dialkylamino,and, if R² and R³ are hydrogen, their physiologicallyacceptable salts with bases, which comprises reacting compounds of theformula II

    R.sup.1 --SO.sub.2 --NR.sup.2 --SO.sub.2 --NR.sup.3 --CO--OR.sup.7 (II)

in which R¹, R² and R³ are as defined above and R₇, with compounds ofthe formula III R⁷ is alkyl, haloalkyl or optionally substituted phenyl,##STR6## in which R⁴, R⁵ and R⁶ are as defined abovein an inert organicsolvent, to give the compounds of the formula I.
 2. The process asclaimed in claim 1, in which R¹ and R² independently of one another are(C₁ -C₃)-alkyl or (C₁ -C₃)-alkenyl, R³ and R⁴ are hydrogen, and R⁵ andR⁶ independently of one another are (C₁ -C₂)-alkyl or (C₁ -C₂)-alkoxy.3. The process as claimed in claim 1, in which R¹ is (C₁ -C₂)-alkyl, R²is (C₁ -C₃)-alkyl or (C₁ -C₃)-alkenyl, R³ and R⁴ are hydrogen, R⁵ ismethyl or methoxy and R⁶ is methyl or methoxy.
 4. The process as claimedin claim 1, in which R⁷ is (C₁ -C₄)-alkyl, (C₁ -C₄)-haloalkyl or phenyl.5. The process as claimed in claim 1, wherein the inert organic solventsemployed are aromatic hydrocarbons, halogenated aromatic hydrocarbons oraprotic polar solvents, or mixtures of the solvents mentioned.
 6. Theprocess as claimed in claim 1, wherein the temperatures at which thereaction is carried out are ranging from 0° C. to the boiling point ofthe solvent employed.
 7. The process as claimed in claim 6, wherein thereaction temperature ranges from room temperature up to 110° C.
 8. Theprocess as claimed in claim 1, wherein the compounds II and III arereacted in a molar ratio of 1:1 to 1.2:1.
 9. The process as claimed inclaim 8, wherein the molar ratio is 1:1 to 1.1:1.
 10. The process asclaimed in claim 1, wherein the process is carried out batchwise orcontinuously.
 11. The process as claimed in claim 5, wherein thecompounds II and III are reacted in a molar ratio of 1:1 to 1.2:1 at atemperature of from 0° C. to the boiling point of the organic solvent.12. The process as claimed in claim 11, wherein the temperature is fromroom temperature to 110° C.
 13. The process as claimed in claim 12,wherein the compounds II and III are reacted in a molar ratio of 1:1 to1.1:1.
 14. The process as claimed in claim 1, wherein R¹ is methyl orethyl, R² is methyl or ethyl, R³ is hydrogen, R⁴ is hydrogen, R⁵ ismethyl, ethyl, methoxy or ethoxy, R⁶ is methyl, ethyl, methoxy or ethoxyand R⁷ is ethyl or phenyl.
 15. The process as claimed in claim 14,wherein R¹ is methyl, R² is methyl, R⁵ is methoxy, R⁶ is methoxy and R⁷is ethyl.
 16. The process as claimed in claim 14, wherein R¹ is methyl,R² is methyl, R⁵ is methoxy, R⁶ is methyl and R⁷ is ethyl.
 17. Theprocess as claimed in claim 14, wherein R¹ is methyl, R² is methyl orethyl, R⁵ is methoxy, R⁶ is methoxy and R⁷ is phenyl.
 18. The process asclaimed in claim 14, wherein R¹ is methyl, R² is methyl or ethyl, R⁵ ismethoxy, R⁶ is methyl and R⁷ is phenyl.
 19. The process as claimed inclaim 14, wherein R¹ is ethyl, R² is methyl or ethyl, R⁵ is ethoxy, R⁶is ethoxy and R⁷ is phenyl.
 20. The process as claimed in claim 14,wherein the solvent is selected from the group consisting of aromatichydrocarbons and halogenated hydrocarbons; the reaction temperature isfrom 20° C. to 110° C.; and compounds II and III are reacted in a molarratio of 1:1 to 1.2:1.
 21. The process as claimed in claim 14, whereinthe solvent is selected from the group consisting of chlorobenzene andtoluene; and compounds II and III are reacted in a molar ratio of 1:1 to1.1:1.